Project Summary We propose to study intergenerational transmission of alcohol, tobacco, and other drug (ATOD) use, including marijuana use, across 3 generations (G1, G2, and G3), and effects of state recreational marijuana legalization (RML) on adolescents? use. We will use a strategy of (1) intensive study of the long-term prospective Three Generational Study (3GS), a community sample consisting of up to two of the biological children (G3) of at-risk adult men (G2) in the Oregon Youth Study (OYS); (2) replications across three studies via collaborations with two other research teams, using data from the Seattle Social Development and Intergenerational Projects (SSDP/TIP) and the Rochester Youth Development and Intergenerational Studies (RYDS/RIGS); and (3) integrative data analysis (IDA) across these 3 studies on up to 1,200 G3 children of diverse socioeconomic, regional, and racial/ethnic backgrounds to answer high-impact questions including on state RML and use of lower prevalence drugs. For OYS/3GS, G1 parents and G2 men (currently ages 41?44 years) were involved since G2 were ages 9-10. The OYS men show high levels of substance use (est. 50% lifetime diagnoses for alcohol dependence or abuse and 50% prevalence of marijuana use in the mid 20s). G2 men, their G3 offspring, and G2 mothers were recruited to 3GS and followed from G3?s early childhood to (for earliest born G3) late adolescence. Specific Aims will be addressed through the collection and analysis of data that will expand the G3 sample size through adolescence in order to examine heterogeneity in growth of ATOD. Multiple indicators of ATOD in G2 and G3 have been and will be assessed to address intergenerational (IG) hypotheses related to IG congruence (similarities across generations in developmental patterns of ATOD use including onset, growth, and influences) versus discontinuity, and to heterogeneity in trajectories of use across adolescence. A dynamic developmental systems approach focusing on both general (e.g., externalizing) and substance-specific (e.g., parent marijuana use) risk factors will be used to trace developmental pathways to precursors (e.g., ATOD awareness), emergent behaviors (experimentation and onset), and regular and escalating ATOD use among individuals followed from early childhood to late adolescence. IG congruence versus discontinuity will be examined in relation to the transmission of contextual risk and problematic behaviors across three generations, and parenting behaviors and peer influences across two generations. Mediators and moderators of IG congruence will be examined, including parent and child gender and factors leading to IG amelioration versus worsening of ATOD use. Regarding RML, within- (pre- to post-RML) and between-child (living in/outside an RML state) effects on marijuana and other ATOD use will be examined, along with moderation of such effects by parent substance use history. The proposed study leverages 3 decades of NIH investment in IG studies to understand and disrupt the familial transmission of ATOD use problems, and quantify the public health impacts of state RML on adolescents from diverse backgrounds.